Location: Virus and Prion ResearchTitle: Biotherapeutics as alternatives to antibiotics: Effects of adenoviral delivered cytokines on innate and adaptive immunity) Author
Submitted to: United States Animal Health Association Proceedings
Publication Type: Abstract only
Publication Acceptance Date: 9/12/2012
Publication Date: N/A
Citation: Interpretive Summary:
Technical Abstract: Acceptable alternatives to the use of antibiotics in food animal practice need to be explored. The use of immunomodulators is a promising area for therapeutic, prophylactic, and metaphylactic use to prevent and combat infectious disease during periods of peak disease incidence. We developed a method to circumvent the need for production of a recombinant cytokine by using a replication-defective adenovirus vector to express cytokines of interest, including interferon-a (IFN-alpha) or porcine granulocyte colony-stimulating factor (G-CSF). Type I interferons, such as IFN-alpha, contribute to innate antiviral immunity by promoting production of antiviral mediators and also play a role in the adaptive immune response. G-CSF enhances neutrophil production and release from the bone marrow and is already licensed for use in humans for treatment of neutropenia and prevention of infections in those with compromised immunity. Porcine reproductive and respiratory syndrome (PRRS) is one of the most devastating and costly diseases to the swine industry world-wide and has been shown to induce a meager IFN-alpha response. Pigs administered the vector expressing porcine IFN-alpha and challenged with PRRSV had lower febrile responses and decreased percentage of lung involvement. Viremia was delayed and there was a decrease in viral load in the sera of pigs. In addition, there was an increase in the number of virus-specific IFN-gamma secreting cells, as well as an altered cytokine profile in the lung 14 days post-infection, indicating that the presence of IFN-alpha at the time of infection can alter innate and adaptive immune responses to PRRSV. Together, these results indicate that IFN-alpha can have protective effects if present during the time of PRRSV infection. Intramuscular administration of the vector expressing porcine G-CSF was found to elicit a sustained neutrophilia, lasting nearly 3 weeks. Thus, it is possible to deliver G-CSF to pigs for a sustained increase in circulating neutrophil numbers in pigs, which may be a useful alternative to antibiotics for prevention of infectious disease, especially during times of stress and pathogen exposure such as post-weaning and post-partum.